Part 2: Why “Scale-Up” Isn’t Just a Bigger Batch
Transitioning a process from discovery scale to GMP manufacturing is almost never straightforward. What runs smoothly at 100 milligrams in the lab can behave very differently at the kilogram scale. Yet too many programs falter because the complexity of this transition is underestimated or treated as a simple “copy and paste” exercise.
The Problem: Thinking Small-Scale Success Guarantees Simple Scale-Up
In discovery, reactions are tested quickly, processes are flexible, and scientists can make rapid adjustments at the bench. But once a molecule moves into GMP manufacturing, the environment changes completely.
At larger scales, every parameter, from solvent recovery and reaction exotherms to impurity profiles and mixing efficiency, can shift in unpredictable ways. Processes that looked efficient at small scale can fail to deliver consistent yield, purity, or safety when scaled up.
The challenge is not only technical but cultural. Many biotechs, pharma companies, and inexperienced CDMOs assume that a strong research process will naturally translate into a manufacturing process. However, at Exemplify BioPharma, we have seen firsthand that without deliberate translation work, scale-up becomes an exercise in trial and error. And in drug development, trial and error costs time, money, and sometimes entire batches.
Why Underestimating Tech Transfer Creates Risk
Underestimating technology transfer does more than slow progress. It creates compounding risk. Each delay pushes timelines, increases cost, and can jeopardize regulatory readiness. In some cases, partners discover too late that a route must be redeveloped because critical parameters were never defined for scale.
For smaller biotech companies in particular, the financial impact of underestimating technology transfer can be significant. GMP manufacturing is one of the most expensive stages of development. A failed scale-up not only wastes material but can delay programs by months, consuming both confidence and cash flow. Smaller biotechs, in particular, often cannot absorb this disruption due to funding milestones that depend on hitting specific timelines.
How to Identify Tech Transfer Risks Before They Escalate
Before committing to a tech transfer plan, ask questions that confirm how deeply your CDMO understands the scaling process. Red flags include:
- Overly simplistic transfer plans: If the proposal assumes that existing lab notebooks or discovery protocols can be used without modification, that is a concern.
- No feasibility testing: A missing intermediate stage for small-scale engineering runs shows a lack of risk planning.
- Limited analytical foresight: If analytical method verification or validation is not included, the data may not withstand GMP scrutiny.
- No mention of material variability: Scale-up magnifies inconsistencies. If raw material variability or impurity fate is ignored, stability problems often follow.
A capable CDMO will explain how process parameters, analytical methods, and material sourcing interact across scales, and they will do so upfront during the proposal and technical scoping conversations. These details determine whether your process survives the transition from lab to plant.
How to Build a Tech Transfer Plan That Reduces Risk and Avoids Surprises
The best way to avoid scale-up surprises is to treat technology transfer as its own project, not just a final step in development.
Start by:
- Building in feasibility runs: Conduct engineering or pilot-scale studies before committing to full GMP batches.
- Integrating analytical validation: Ensure that methods are verified and suitable for scaled production, not just bench-scale work.
- Characterizing your process early: Identify critical quality attributes and define control strategies before manufacturing begins.
- Encouraging open communication: Create a shared understanding of what success means at scale, including acceptable ranges, risks, and contingency plans.
Successful tech transfer is not about over-engineering. It is about foresight and preparation. It is about identifying the gaps between research and manufacturing and bridging them through structured planning and collaboration.
Our Perspective
At Exemplify BioPharma, a Symeres company, we have supported many programs through this critical transition. Our teams have seen what happens when scale-up is treated as a simple step instead of a dedicated process, and we have helped biotech and pharma companies recover from it.
By combining process chemistry, analytical, and formulation expertise in one partnership, we ensure that development and manufacturing decisions are made together. Each scale-up plan is tested for real-world performance, giving partners confidence that what works in the lab will work in production.
Scaling up is not just about making more material. It is about maintaining integrity, reproducibility, and regulatory readiness at every level. With the right partner, technology transfer becomes a bridge to success rather than a stumbling block.
Next in the Series: Regulatory Shortfalls and Misalignment – When Technical Excellence Isn’t Enough. If you’d like to explore all five red flags in depth, read our full whitepaper: 5 CDMO Red Flags You Can’t Ignore: A Guide for Biotechs and Pharma
